The c.605T>G variant in the glucokinase gene, GCK, causes an amino acid change of methionine to arginine at codon 202 (p.(Met202Arg)) of NM_000162.5. GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.873, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in 39 unrelated individuals with hyperglycemia (PS4; PMID: 30259503, 29927023, 29510678, 29207974, 29056535, 27256595, 25953829, 25555642, 24918535, 20337973, 19309449, 11508276, internal lab contributors). This variant was identified in an individual with a clinical history highly specific for GCK-hyperglycemia (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and three-generation, dominant family history of diabetes or hyperglycemia in a family not used for PP1) (PP4_Moderate; internal lab contributors). This variant segregated with diabetes/hyperglycemia, with 13 informative meioses in one family with MODY (PP1_Strong; internal lab contributors). Another missense variant, c.571C>T p.(Arg191Trp), has been classified as pathogenic by the ClinGen MDEP but has a greater Grantham distance than p.(Arg191Gln) (PM5_Supporting). In summary, c.572G>A meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PP3, PP2, PM2_Supporting, PS4, PP1_Strong, PP4_Moderate, PM5_Supporting.